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Case report 1
A case of a boy whose teeth had fallen out a bit earlier
Dagmar Procházková
Clinical genetics – practise (aVLKGC7X1)

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Clinical genetics – practise (aVLKGC7X1)
Learning outcomes
̶the student will be presented with a case report of a child with hypophosphatasia

Adobe Systems
Clinical genetics – practise (aVLKGC7X1)
̶The case of a boy whose teeth fell out at the age of 18 months.
Usually the baby has all baby teeth at 30 months of age.

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Clinical genetics – practise (aVLKGC7X1)
History
̶Family history: without interest
̶The child from the 1st pregnancy, delivery in the 35 th week of pregnancy, birth weight 2060g,
birth length 47 cm. Postpartum adaptation in the norm, breastfed for a full month, then artificial
nutrition. From the 4 th month of age mixed baby food.
̶He prospered well, psychomotor development normal.
̶With verticalization gradually lower limbs pain, development of genua and crura vara, chest with
steep ribs with regular administration of vitamin D. At the age of 18 months, the first deciduous
teeth (lower incisors and canines) begin to fall out.

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Clinical genetics – practise (aVLKGC7X1)
̶Long-term care of a dentist, complete dental prosthesis from 3 years of age, in adulthood
gradually permanent teeth replaced by dental prosthesis.
̶
̶From toddler age in the care of an orthopedist.
̶
̶X-ray of the wrist and hand in childhood: thin bone structure, in the distal metaphysis of the
radius and ulna at the epiphysis oval brightening.
̶
̶Bone densitometry at the age of 15: in the lumbar spine and in the whole-body scan - osteopenia.
At present the finding is improved, in both localities the finding of normal bone density in the
tolerated zone to age with an increase in BMD (bone mineral density) in the spine and the hip in
general.

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Clinical genetics – practise (aVLKGC7X1)
̶At 19-23 years of age, valgus osteotomy of the lower limbs was performed. However, even after
correction, lower limbs pain persists.
̶Fractures
̶
̶10/2014 right leg, fracture of the second metatarsus
̶
̶6/2016 right hand, fracture of the base of the fifth metatarsus
̶
̶8/2016 left foot, fracture of the diaphysis of the third metatarsus
̶
̶

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Clinical genetics – practise (aVLKGC7X1)
̶As a child, he thrived on weight well. The height to age gradually decreased below the 3rd
percentile. The final height of the figure in adulthood is 166 cm.
̶
̶In ultrasound of the abdomen without signs of nephrocalcinosis, detected renal cyst 16x11 mm
stationary with age.
̶
̶Renal function has long been normal.

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Clinical genetics – practise (aVLKGC7X1)
Selected laboratory results
Parameter
Normal value
Results
Comment
Ca
2,15-2,6 mmol/l
Repeatedly in the norm

Ca ++
1-1,4 mmol/l
1,264 mmol/l

P
1,1-1,9 mmol/l (children); 0,8-1,45 mmol/l (adults)
In childhood 2,18...2,4 mmol/l; in adulthood 1,52 mmol/l
Elevated values
ALP
0,67-2,15 μkat/l
0,23...0,36...1,45...0,51...1,37...0,69...0,82...1,19 μkat/l
Fluctuating values
ALP isoforms

hepatic 3 %
bone 95 %
intestinal 2 %

25-OH vitamin D
50-200 nmol/l
21,5 nmol/l
Decreased values
Parathyroid hormone
0,8-7,8 pmol/l
0,81…0,5…2,7 pmol/l
Fluctuating values
osteokalcin NMID
14-46 μg/l
60…68...169,4 μg/l
Elevated values
calcitonin
0-18,2 ng/l
5,00…2,00 ng/l

Ca in urine/24 hours
2,4-7,5 mmol/24 hours
3,6 mmol/24 hours

Ca/creatinine in urine
0-0,6
0,23

P in urine/24 hours
16-33,5 mmol/24 hours
33,4 mmol/24 hours

phosphoethanolamine (PEA) in urine
9-25 mmol/molKr
104 mmol/molKr
Elevated values

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Clinical genetics – practise (aVLKGC7X1)
Laboratory examination in adulthood (General Hospital Prague):
̶
̶↑ Pyridoxal-5-phosphate (PLP), vitamin B6 in the blood 2121.0 (3.6-18.0) µg/l
̶
̶↑ Urinary phosphoethanolamine (PEA) 42 (norm up to 10.0) mmol / molKr

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Clinical genetics – practise (aVLKGC7X1)
DNA diagnostics
̶In 2016, DNA analysis of the ALPL gene for HPP was performed at the Institute of Biology and
Medical Genetics of the 2nd Medical Faculty of Charles University and the Motol University
Hospital.
̶
̶Proband is a composite heterozygote for the c.526G> A, p. (Ala176Thr) / c.2797_802delCCCACT, p.
(Ser266_His267del) mutations.
̶
̶Both variants are termed pathogenic and are the molecular cause of HPP (Taillandier, 2000;
Spetchian, 2006).

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Clinical genetics – practise (aVLKGC7X1)
Hypophosphatasia- HPP
̶# MIM 241500, 241510, 146300
̶Rare congenital metabolic disorder caused by a mutation in the ALPL gene, which encodes tissue
non-specific alkaline phosphatase (TNSALP)
̶Low serum TNSALP activity leads to impaired skeletal and dental mineralization
̶The incidence of severe forms in the European population is about 1: 300,000 live births, milder
forms are more common
̶Heredity in severe forms AR, in lighter forms AD
̶The clinical manifestation is very wide

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Clinical genetics – practise (aVLKGC7X1)
Hypophosphatasia - HPP-forms
̶Distribution based on the severity of clinical symptoms and age of the individual at the time of
the first manifestation of the disease:
̶Perinatal lethal - already intrauterinely as severe skeletal hypomineralization
̶Prenatal benign - short and markedly curved bones of the lower limbs, improvement in the
3rd trimester of pregnancy
̶Infantile - in the first 6 months of age, deformities of the chest, ribs, hypercalcaemia,
nephrocalcinosis, convulsions, failure to thrive, craniosynostosis, pyridoxine-responsive epilepsy
̶Pediatric - manifestations after 6 months of age, changes resembling rickets, skeletal
deformities, short stature, dentition disorders, failure to thrive, hypotension, myopathy, pain of
low extremities

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̶Adult - fractures, pseudofractures, limb pain, osteoarthropathy, chondrocalcinosis
̶
̶Odontohypophosphatasia-exclusively dental symptoms, premature loss of teeth, increased caries,
mildest form

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Clinical genetics – practise (aVLKGC7X1)
Diagnostics
̶Diagnosis is based on clinical symptoms typical of individual forms of HPP (HPP can be diagnosed
in utero in the perinatal form by ultrasound, possibly X-ray).
̶Blood calcium levels are usually normal, there may be hypercalcaemia. Blood phosphorus levels tend
to be elevated.
̶Decreased ALP in the blood is typical. In some cases, ALP can reach low or cut-off values even
with HPP carriers. Age-specific standards should be used to evaluate blood ALP.
̶In patients with HPP, concentrations of pyridoxal-5-phosphate in the blood and phosphoethanolamine
in urine are high, indicating ALP dysfunction.
̶Molecular genetic analysis of the ALPL gene confirms the disease.

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Clinical genetics – practise (aVLKGC7X1)
Hypophosphatasia- HPP
̶Causal therapy:
̶Recombinant TNSALP Enzyme Replacement Therapy, Alpha Phosphatase, StrensiqTM, Alexion
Pharmaceuticals
̶
̶Reserved for severe forms of HPP, very expensive
̶
̶Other options: ????? calcium, vitamin D, bisphosphonates ?????
̶Not recommended

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Take home message
̶In dentistry, too, we must keep in mind the inherited metabolic disorders
Clinical genetics – practise (aVLKGC7X1)

Lékařská fakulta Masarykovy univerzity
2021
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