SHORT TERM OUTCOME OF LCHAD DEFICIENCY IDENTIFIED BY NEWBORN SCREENING.

Alvaro Serrano Russi MD1

1Stead Department of Pediatrics; Division of Medical Genetics; University of Iowa, Iowa City, IA, USA E-mail: Alvaro-serranorussi@uiowa.edu

Phone: 319-356-2674

Patient was born at 38 weeks gestation with a birth weight of 2175 grams. APGAR scores of 8 and 9. She was small for gestational age and was found to have persistently decreased body temperatures associated with blood glucose values of 34 mg/dL to 64 mg/dL but dropping to 50 mg/dL with minimal fasting interval. Newborn screening collected at 24 hours showed elevations in C14-OH, C16-OH, C16:1-OH and C18-OH.

Liver function testing and abdominal right upper quadrant ultrasound were normal. Echocardiogram showed normal function. She was managed locally with frequent feeding and was started on a mixture of breast milk and formula containing 55% MCT oil. Confirmatory testing in the first week of life showed elevations of C16 and C18

3-hydroxyacylcarnitine with an initial free carnitine of 20 nmol/mL. Urine organic acids showed hypoketotic C6-C10 dicarboxylic aciduria and a 3-hydroxydicaboxylic aciduria. Molecular genetic testing showed the homozygous c.1528G>C mutation in HADHA. No mutation was found in HADHB.

At 5 months with acute illness and decreased oral intake, she had significantly elevated transaminases and CPK (AST: 514 U/L; ALT: 213 U/L; CPK: 8503 U/L) decreasing over five days of illness while following emergency protocol.

Baseline ocular exam at 6 months did not show evidence of retinopathy. Most recent clinic visit at 8 months showed she had recovered and was developmentally normal. Solid food was added on at 5-6 months of age monitoring levels of hydroxylated acyl carnitines and essential fatty acids.

Age 3 days 36 days 62 days 15 weeks 5 months 9 months Reference
C12-OH 0.17 0.04 0.02 0.03 0.04 0.02 <0.09
nmol/mL
C14:1OH 0.21 0.05 0.03 0.06 0.06 0.02 <0.18
nmol/mL
C14-OH 0.31 0.07 (H) 0.03 0.06 (H) 0.05 (H) 0.03 <0.05
nmol/mL
C16:1-OH 0.31 0.07 0.04 0.06 0.06 0.04 <0.36
nmol/mL
C16-OH 0.77 0.21 (H) 0.09 (H) 0.16 (H) 0.13 (H) 0.11 (H) <0.07
nmol/mL
C18:2-OH 0.31 0.12 (H) 0.08 (H) 0.14 (H) 0.18 (H) 0.08 (H) <0.06
nmol/mL
C18:1-OH 1.40 0.37 (H) 0.17 (H) 0.34 (H) 0.36 (H) 0.19 (H) <0.04
Total 3.48 0.93 0.46 0.85                     0. 88 nmol/mL

0.49

Follow up of hydroxylated long chain acyl carnitines over time