INDICANURIA:

HARTNUP DISEASE
CASE BACKGROUND: HISTORY
• Patient is a neonate of healthy consanguineous parents presented
with:
• Malabsorption diarrhea
• Metabolic acidosis
• Hepatopathy
• Recurrent hypoglycemia
• Bluish discoloration of the diaper was also noted at several occasions
• No family history of endocrine, nutritional or metabolic disease
PHYSICAL EXAMINATION
• Weight: 3580 grams
• Length: 50 cm
• Head circumference: 37.5 cm
• Apgar score: 7/9/10
SIGNS AND SYMPTOMS
• During 2nd day of life:
• Developed hypoglycemia
• Next days:
• Child developed diarrhea
• Metabolic acidosis
• Elevated transaminases
• Inadequate weight gain
• Hypercalcemia
REASON FOR ADMISSION
• Patient is a 2 day old neonate - Abnormal levels of blood sugar
followed by diarrhea and metabolic acidosis
Genetic assessment
• Sanger sequencing: Heterozygous inheritance - confirmed
homozygous state in patient (parents are heterozygous carriers)
 Laboratory Findings
• Umbilical cord pH: 7.27
• Blood sugar level – 14 mg/dL (hypoglycemic)
• Diarrhea
• Metabolic acidosis - (base excess – 14 mmol/L)
• Elevated transaminses:
• Glutamic oxaloacetic transaminase: 219 U/L [normal: <79]
• Glutamic pyruvate transaminase: 118 U/L [normal: <48]
• Persistent bluish discoloration of urine spots
• Increased serum proinsulin levels: (330 pmol/L [normal: <11]) – peptide hormone
processing
• Elevated thyrotropin levels – (maximum: 13.2 µU/mL [normal: 1.36-8.76])
• Low free thyroxine levels - (minimum: 8.3 pg/mL [normal: 10.8 – 20.3])
Laboratory tests
• Ultra-performance liquid chromatography–electrospray ionization–
tandem mass spectrometry
ULTRA-PERFORMANCE LIQUID CHROMATOGRAPHY–
ELECTROSPRAY IONIZATION–TANDEM MASS
SPECTROMETRY
DIAGNOSIS
• Indigo urine spots - Highest concentrations of indigo derivatives during 1st
week of life
• Prohormone convertase 1/3 deficiency – detection of massively increased
serum proinsulin levels
• Altered kinetics of insulin metabolism – episodes of hypoglycemia (2.4 –
3.0 U/L [normal: <2])
• Hypothyroidism – elevated thyrotropin levels and low free thyroxine level
• Hypoparathyroidism – (1.0 pmol/L; normal: 1.6-6.9) with increased serum
phosphate (2.22 mmol/L; normal: 1.15-2.15)
• Obesity – weight: 11.9 kg, BMI: 20.3