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Novel Mutations in the CPT1A Gene Identified in the Patient Presenting Jaundice as the First Manifestation of Carnitine Palmitoyltransferase 1A Deficiency.

Choi JS, Yoo HW, Lee KJ, Ko JM, Moon JS, Ko JS - Pediatr Gastroenterol Hepatol Nutr (2016)

Bottom Line: From direct sequencing analysis of CPT1A, two novel mutations, c.1163+1G>A and c.1393G>A (p.Gly465Arg), were identified.High glucose infusion rate was required for recovery of his vital signs and mentality.Diet rich in high carbohydrate, low fat and inclusion of medium chain triglyceride oil resulted in improvement in cholestatic hepatitis and since then the boy has shown normal growth velocity and developmental milestones to date.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
Carnitine palmitoyltransferase 1A (CPT1A) is an enzyme functioning in mitochondrial fatty acid oxidation (FAO) of the liver. Patients with CPT1A deficiency have impaired mitochondrial FAO and display hypoketotic hypoglycemia and hepatic encephalopathy as typical manifestations. In this report, we present a case of CPT1A deficiency presenting jaundice as the first manifestation. A 1.9 years old boy showed jaundice and elevated levels of free and total carnitine were observed. From direct sequencing analysis of CPT1A, two novel mutations, c.1163+1G>A and c.1393G>A (p.Gly465Arg), were identified. At the age of 2.2 years, hypoglycemia, tachycardia, and altered mental status developed just after cranioplasty for craniosynostosis. High glucose infusion rate was required for recovery of his vital signs and mentality. Diet rich in high carbohydrate, low fat and inclusion of medium chain triglyceride oil resulted in improvement in cholestatic hepatitis and since then the boy has shown normal growth velocity and developmental milestones to date.

No MeSH data available.


Related in: MedlinePlus

Hepatomegaly and nephromegaly was observed onin ultrasonographic examinationy performed at age 1.9 years.
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Figure 1: Hepatomegaly and nephromegaly was observed onin ultrasonographic examinationy performed at age 1.9 years.

Mentions: During examination at our hospital, jaundice appeared on his face and abdomen, icteric sclera and scaphocephaly were observed. The height and weight of the boy were 85 cm (25-50th percentile) and 10.7 kg (3-5th percentile), respectively and his head circumference was 49.7 cm (50-75th percentile). He could walk alone and walk up and down the staircase. Moreover, he could speak many meaningful words. The liver was palpable 4 cm below the right costal margin. The findings of initial laboratory examination performed in our hospital, revealed elevated levels of bilirubin and liver enzymes: total bilirubin, 8.0 mg/dL (normal 0.2-1.2 mg/dL); direct bilirubin, 5.7 mg/dL (normal 0-0.5 mg/dL); aspartate aminotransferase (AST), 234 IU/L (normal 1-40 IU/L); alanine transaminase (ALT), 168 IU/L (normal 1-40 IU/L); and alkaline phosphatase, 480 IU/L (normal 60-300 IU/L). Viral hepatitis serology markers including hepatitis A, B, and C viruses, cytomegalovirus, and Epstein-Barr virus were not informative with respect to diagnosis. Prothrombin time and activated partial thromboplastin time) were 13.6 sec (normal 9.6-12.5 sec) and 48.1 sec (normal 26-35.3 sec), respectively. Serum ammonia level was 89 µkg/dL (normal <75 µg/dL). Hemoglobin was 8.2 g/dL (normal 10.5-14.0 g/dL) and iron deficiency (iron 53 µg/dL, normal 50-170 µg/dL; total iron-binding capacity 479 µkg/dL, normal 280-400 µg/dL; ferritin 8.8 ng/mL, normal 10-300 ng/mL) was noted with no definite evidence of hemolysis. Ceruloplasmin, creatine phosphokinase, and lactate dehydrogenase levels were normal. Compensated metabolic acidosis with normal anion gap (pH 7.38; HCO3-, 18.3 mmol/L; Na, 136 mmol/L; Cl- 103 mmol/L) was found on blood gas and electrolyte analyses, and the presence of renal tubular acidosis (RTA) was suggested. Tubular dysfunctions including mild tubular proteinuria were observed (spot urine ratio of beta-2 microglobulin/creatinine 1.52 µg/mg, normal 0.09-0.48 µg/mg; N-acetyl-beta-glucosaminidase/creatinine 206 IU/g, normal 2.9-20.0 IU/g; protein/creatinine 0.23 mg/mg, normal <0.3 mg/mg). Abdominal ultrasonography revealed hepatomegaly with coarse parenchymal echogenicity without focal lesion or bile duct dilatation. Enlarged kidneys with increased renal cortical echogenicity were also observed (Fig. 1). Skull simple radiography and three-dimensional computed tomography images showed premature closure with sclerotic change of the sagittal suture, suggesting craniosynostosis (Fig. 2).


Novel Mutations in the CPT1A Gene Identified in the Patient Presenting Jaundice as the First Manifestation of Carnitine Palmitoyltransferase 1A Deficiency.

Choi JS, Yoo HW, Lee KJ, Ko JM, Moon JS, Ko JS - Pediatr Gastroenterol Hepatol Nutr (2016)

Hepatomegaly and nephromegaly was observed onin ultrasonographic examinationy performed at age 1.9 years.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4821986&req=5

Figure 1: Hepatomegaly and nephromegaly was observed onin ultrasonographic examinationy performed at age 1.9 years.
Mentions: During examination at our hospital, jaundice appeared on his face and abdomen, icteric sclera and scaphocephaly were observed. The height and weight of the boy were 85 cm (25-50th percentile) and 10.7 kg (3-5th percentile), respectively and his head circumference was 49.7 cm (50-75th percentile). He could walk alone and walk up and down the staircase. Moreover, he could speak many meaningful words. The liver was palpable 4 cm below the right costal margin. The findings of initial laboratory examination performed in our hospital, revealed elevated levels of bilirubin and liver enzymes: total bilirubin, 8.0 mg/dL (normal 0.2-1.2 mg/dL); direct bilirubin, 5.7 mg/dL (normal 0-0.5 mg/dL); aspartate aminotransferase (AST), 234 IU/L (normal 1-40 IU/L); alanine transaminase (ALT), 168 IU/L (normal 1-40 IU/L); and alkaline phosphatase, 480 IU/L (normal 60-300 IU/L). Viral hepatitis serology markers including hepatitis A, B, and C viruses, cytomegalovirus, and Epstein-Barr virus were not informative with respect to diagnosis. Prothrombin time and activated partial thromboplastin time) were 13.6 sec (normal 9.6-12.5 sec) and 48.1 sec (normal 26-35.3 sec), respectively. Serum ammonia level was 89 µkg/dL (normal <75 µg/dL). Hemoglobin was 8.2 g/dL (normal 10.5-14.0 g/dL) and iron deficiency (iron 53 µg/dL, normal 50-170 µg/dL; total iron-binding capacity 479 µkg/dL, normal 280-400 µg/dL; ferritin 8.8 ng/mL, normal 10-300 ng/mL) was noted with no definite evidence of hemolysis. Ceruloplasmin, creatine phosphokinase, and lactate dehydrogenase levels were normal. Compensated metabolic acidosis with normal anion gap (pH 7.38; HCO3-, 18.3 mmol/L; Na, 136 mmol/L; Cl- 103 mmol/L) was found on blood gas and electrolyte analyses, and the presence of renal tubular acidosis (RTA) was suggested. Tubular dysfunctions including mild tubular proteinuria were observed (spot urine ratio of beta-2 microglobulin/creatinine 1.52 µg/mg, normal 0.09-0.48 µg/mg; N-acetyl-beta-glucosaminidase/creatinine 206 IU/g, normal 2.9-20.0 IU/g; protein/creatinine 0.23 mg/mg, normal <0.3 mg/mg). Abdominal ultrasonography revealed hepatomegaly with coarse parenchymal echogenicity without focal lesion or bile duct dilatation. Enlarged kidneys with increased renal cortical echogenicity were also observed (Fig. 1). Skull simple radiography and three-dimensional computed tomography images showed premature closure with sclerotic change of the sagittal suture, suggesting craniosynostosis (Fig. 2).

Bottom Line: From direct sequencing analysis of CPT1A, two novel mutations, c.1163+1G>A and c.1393G>A (p.Gly465Arg), were identified.High glucose infusion rate was required for recovery of his vital signs and mentality.Diet rich in high carbohydrate, low fat and inclusion of medium chain triglyceride oil resulted in improvement in cholestatic hepatitis and since then the boy has shown normal growth velocity and developmental milestones to date.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
Carnitine palmitoyltransferase 1A (CPT1A) is an enzyme functioning in mitochondrial fatty acid oxidation (FAO) of the liver. Patients with CPT1A deficiency have impaired mitochondrial FAO and display hypoketotic hypoglycemia and hepatic encephalopathy as typical manifestations. In this report, we present a case of CPT1A deficiency presenting jaundice as the first manifestation. A 1.9 years old boy showed jaundice and elevated levels of free and total carnitine were observed. From direct sequencing analysis of CPT1A, two novel mutations, c.1163+1G>A and c.1393G>A (p.Gly465Arg), were identified. At the age of 2.2 years, hypoglycemia, tachycardia, and altered mental status developed just after cranioplasty for craniosynostosis. High glucose infusion rate was required for recovery of his vital signs and mentality. Diet rich in high carbohydrate, low fat and inclusion of medium chain triglyceride oil resulted in improvement in cholestatic hepatitis and since then the boy has shown normal growth velocity and developmental milestones to date.

No MeSH data available.


Related in: MedlinePlus