Table 1. Clinical data of patients with ATP6AP2 mutations
ParameterPatient 1Patient 2Patient 3
SexMaleMaleMale
Current age17 yr21 yr10 mo
ConsanguinityNoneNoneNone
EthnicityCaucasianCaucasianCaucasian
Mutation cDNAc.293C>Tc.212G>Ac.212G>A
Mutation proteinp.Leu98Ser (L98S)p. Arg71His (R71H)p. Arg71His (R71H)
Glycosylation defectIEF: tetrasialotransferrin: 34.2% (norm: 48.5–65.3%); trisialotransferrin: 28.9% (norm: 5.5–15.1%); disialotransferrin: 15% (norm: 2.0–6.1%); monosialotransferrin: 3.3% (norm: 0.0–3.7%); asialotransferrin: 1.5% (norm: 0%)HPLC: tetrasialotransferrin 55.17% (norm: 85.7–94.0%); trisialotransferrin 33.11% (norm: 1.16–6.36%); disialotransferrin 8.92% (norm: 0.38–1.82%); monosialotransferrin 1.68% (norm: 0%)HPLC: tetrasialotransferrin 35.7% (norm: 85.7–94.0%); trisialotransferrin 36.4% (norm: 1.16–6.36%); disialotransferrin 18.7% (norm: 0.38–1.82%); monosialotransferrin 9.0% (norm: 0%)
Onset of symptoms5 moDirectly after birthDirectly after birth
LiverProlonged neonatal jaundice and persistent hepatosplenomegaly with recurrent episodes of hypoalbuminemia and ascitesNo hepatomegaly in childhood, but liver parenchyma of an inhomogeneous, hyperechoic structure.Prolonged neonatal jaundice and hepatosplenomegaly. Cholestasis. Irregular liver parenchyma with portosystemic shunts and ascites. Hypoalbuminemia, hyperammonemia. Coagulopathy. Listed for liver transplantation.
Today: hepatomegaly, mild elevation of liver enzymes
Liver biopsyMicronodular hepatic cirrhosis with moderate macrovesicular steatosis (biopsy at 8 mo), elevated copperNot availableDiffuse micronodular hepatic cirrhosis
Elevated copper
Neonatal icterus+-+
Splenomegaly+++
InfectionsRecurrent severe infections (e.g., sepsis, peritonitis)Recurring pulmonary and upper respiratory tract infections throughout infancy and childhoodRecurring upper respiratory tract infections, positive blood cultures with pneumococcus at one occasion
Neurological symptomsMild cognitive impairmentAtaxic gait, mild cognitive impairmentNormal
Cutis laxaMild to moderatePronounced, improvement over timePronounced
Hypogammaglo-bulinemia++-
IgG2.31 g/L (reference: 5.6–13.8 g/L)Reduced IgG1 and IgG3-
IgM<0.17 g/L18 mg/dl (reference: 40–230 mg/dl)-
IgA<0.08 g/L<15 mg/dl (reference: 70–400 mg/dl)-
Increased transaminasesAt 17 yr, mild elevation of transaminases (AST 61 U/l [reference: 15–46 UI/l], ALT 51 U/l [reference: 10–40 U/l])Ranging from mild elevation at age 9 yr: AST 92 U/l (reference: 8–60 U/l), ALT 59 U/l (reference: <44 U/l) to pronounced hepatic affection (AST 135 U/l)Within the first year: AST 100–160 U/l, (reference: <71 U/l)
Serum copperNot availableAt 1 yr: 1.5 µmol/l (reference: 10–30 µmol/l)Normal serum copper at the age of 4 mo: 89 µg/dl (reference: 65–165 µg/dl)
Normalized over the following months
Serum lipidsAt age 17 yr (liver normal):At age 20 yr:At age 5 mo:
Cholesterol: 172 (reference: 200 mg/dl)Cholesterol: 199 (reference: 200 mg/dl)Cholesterol: 254 (reference: 81–147 mg/dl)
LDL-cholesterol: 90 (reference: 50–130 md/dl)LDL-cholesterol: 149 (reference: 50–130 md/dl)
Other laboratory findingsLow factor V and VILow factor XI (58% [reference: >70%]) and free protein S (57.5% [reference: 60–140%])Low factors II (27.7% [reference: 60–120%]), V (35.9% [reference: 55–130%]), VII (21.9% [reference: 47–130%]), IX (17.27% [reference: 36–136%]), and XI (23.9% [reference: 49–134%])
Factor V: 30% (reference: 65–148%), factor VII: 24% (reference: 58–115%)
Other clinical findingsMild dysmorphic featuresLow-set ears, micrognathia, a flat and wide-set chest, laterally facing nipples, and hypospadia

IEF, isoelectric focusing.